A-TANGO Phase 2 Study

NCT06890039 | Not Yet Recruiting Phase 2 DMC

• 4 other identifiers: G-TAK-ES-019450962022-000128-391005490
• Study Type: interventional
• Target: 78
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this research is to know if a new combination of drugs (TAK-242 and G-CSF) in combination with standard therapy for acute-on-chronic liver failure (ACLF) is more effective than standard therapy for ACLF treatment and is safe. Description of the population to be studied: ACLF is a syndrome that occurs in patients with chronic liver disease, with or without previously diagnosed cirrhosis, which is characterized by acute hepatic decompensation. Cirrhosis is a chronic disease of the liver marked by degeneration of cells, inflammation, and thickening and scarring (fibrosis) of liver tissue. Hepatic decompensation is a sudden decline in liver function. It is characterized by severe liver damage and complications like jaundice (yellowing of the skin or whites of the eyes), ascites (a condition where excess fluid accumulates in the abdominal cavity and in abdominal organs) and encephalopathy (a group of symptoms that result from damage or dysfunction in the brain, causing a range of cognitive and neurological impairments). It may result in liver failure, one or more organ failures other than liver (renal, brain, coagulation, respiratory, cardiovascular), and is associated with increased mortality within 28-days and up to 3 months from onset. Grade 1 ACLF has a \>15% risk of mortality at 28 days. Purpose of the study: The investigational medication, TAK-242, is aimed at stopping an "over-reaction" of the immune system (the body's defense system) while G-CSF encourages your liver cells to grow. In patients with severe inflammation of the liver due to alcohol \[severe alcoholic hepatitis (sAH)\] and ACLF, this over-reaction may cause the liver and other organs in the body to suddenly stop working (organ failure). The hypothesis of the study is that by blocking this over-reaction and encouraging your liver cells to grow your condition may improve.

Conditions

Acute-On-Chronic Liver Failure; Alcoholic Hepatitis; Liver Cirrhosis, Alcoholic

Keywords

Novel combinatorial therapy; Improve hepatocyte proliferation; ACLF; Liver disease

Outcome Measures

Primary Outcomes (1)

• To assess the safety of TAK-242 in combination with G-CSF and alone in subjects with sAH and ACLF compared to placebo

  To assess the safety of TAK-242 in combination with G-CSF (G-TAK) and alone in subjects with sAH and ACLF compared to placebo from baseline to Day 14: * The percentage of subjects who experience at least 1 treatment-emergent AE (TEAE) or SAE. * The percentage of subjects who discontinue the study drug due to an AE (including methemoglobinemia).

  Baseline to Day 14

Secondary Outcomes (14)

• Changes in CLIF-C OF score

  Baseline to Day 14

• Changes in CLIF C ACLF-CRP score

  Baseline to Day 84

• Pharmacokinetics parameters for TAK-242 along with its two main metabolites and G-CSF

  Baseline to Day 7

• To Investigate the effects of TAK-242 alone or in combination with G-CSF, compared with placebo and between active treatment groups, on key biomarkers for inflammation, cell death, liver function, regeneration and senescence

  From Baseline to Day 4, 7, and 14

• To investigate transplant free and overall survival in subjects with sAH and ACLF

  Upto Day 84

Study Arms (3)

Standard of care (SOC) plus placebo for TAK-242 plus placebo for G-CSF

PLACEBO COMPARATOR

Drug: Placebo

Standard of care (SOC) plus TAK-242 plus placebo for G-CSF

ACTIVE COMPARATOR

Drug: TAK-242

Standard of Care (SOC) plus TAK-242 plus G-CSF

ACTIVE COMPARATOR

Drug: TAK-242; Drug: G-CSF (Filgrastim)

Interventions

Placebo DRUG

Matching placebo for TAK-242: 5% dextrose solution and commercially available 20% intralipid (prepared by hospital pharmacy staff) Matching placebo for G-CSF: identical to vehicle for filgrastim (prepared for injection by hospital pharmacy staff)

Standard of care (SOC) plus placebo for TAK-242 plus placebo for G-CSF

TAK-242 DRUG

TAK-242 concentrate for solution for infusion (80 mg/ mL in 3 mL ethanol) ): 240 mg TAK-242 per vial. To be reconstituted with 5% dextrose (36 mL) and commercially available 20% intralipid (21 mL). TAK-242) will be administered as a continuous IV infusion starting with a loading dose of 0.9 mg/kg administered over 30 minutes, followed by a continuous, constant rate infusion of 1.8 mg/kg/day for 10 days. PLUS placebo for G- CSF

Standard of Care (SOC) plus TAK-242 plus G-CSF; Standard of care (SOC) plus TAK-242 plus placebo for G-CSF

G-CSF (Filgrastim) DRUG

Commercially available vials for subcutaneous injection. Quantitative composition (per mL): Filgrastim: 300 mcg Acetate: 0.59 mg Sorbitol: 50.0 mg Tween® 80: 0.04 mg Sodium: 0.035 mg Water for Injection USP q.s. ad 1.0 mL G-CSF will be given subcutaneously once daily at a dose of 5 µg/kg for 5 days (Day 1-5) and at Day 8 (6 injections in total)

Standard of Care (SOC) plus TAK-242 plus G-CSF

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects ≥18 of age and ≤75 years of age
• Compliance with acceptable contraceptive methods.
• With a diagnosis of severe alcoholic hepatitis that is resistant to steroid therapy as defined by a Lille score of \>0.45 and/or in whom steroids are contraindicated.
• Eligible subjects will have Grade 1-3 ACLF with a maximum of three organ failures using the CLIF-C OF score AND the CLIF-C ACLF-CRP score of \>35 and \<60.

You may not qualify if:

• Patients with any of the following criteria are to be excluded:
• Refusal to give informed consent
• Mechanical ventilation due to respiratory failure and/or need for renal replacement therapy and or requiring inotropes for circulatory support with a noradrenaline requirement of \>0.5ug/kg/min to maintain mean arterial pressure \> 70mmHg
• Subject has received any investigational drug within 30 days of randomization
• Subject has any of the following conditions:
• history of liver transplantation
• postoperative decompensation after partial hepatectomy
• liver failure without underlying chronic liver injury
• Any untreated infections (\<48h antibiotic therapy) including gram-positive infections, active tuberculosis or coinfection with HIV.
• Chronic or pre-existing kidney failure, survival prognosis of \<6 months due to severe co-morbid conditions that might confound study results or compromise subject safety
• Methemoglobinemia, clinically-significant disseminated intravascular coagulation, uncontrolled bleeding, sickle cell anemia
• Uncontrolled seizures, Creutzfeldt-Jakob disease, glucose-6-phosphate dehydrogenase deficiency.
• Active malignancy, premalignant hematological disorders (e.g., myelodysplastic syndrome, chronic myeloid leukemia) or multiorgan failure (≥ 4 organ failures).
• Pregnancy or nursing women
• Allergy to eggs

Sponsors & Collaborators

• Yaqrit Ltd: lead
• European Foundation for Study of Chronic Liver Failure: collaborator
• University College, London: collaborator
• HEPYX LIMITED: collaborator
• CROWDHELIX LIMITED: collaborator
• Charite University, Berlin, Germany: collaborator
• University of Leipzig: collaborator
• Concentris research management gmbh: collaborator
• Assistance Publique - Hôpitaux de Paris: collaborator
• Leiden University Medical Center: collaborator
• INTERNATIONAL MARKET ACCESS CONSULTING GMBH: collaborator
• KlinEra Global Services: collaborator
• European Association for the Study of the Liver: collaborator
• EUROPEAN LIVER PATIENTS' ASSOCIATION: collaborator

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure; Hepatitis, Alcoholic; Liver Cirrhosis, Alcoholic; Liver Diseases

Interventions

ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Digestive System Diseases; Hepatitis; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Central Study Contacts

Monica Razdan

CONTACT

+917045561443; monica.razdan@klinera.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The investigational drug blind is maintained by study drug/placebo preparation by an unblinded person (hospital pharmacist, or equivalent). The study drug blind shall not be broken by the investigator unless information concerning the study drug is necessary for the medical treatment of the subject.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is randomized, double-blind, and placebo-controlled to avoid subjective bias in the assessment of the study drug. Placebo will be administered as a control in order to establish the frequency or magnitude of changes in clinical endpoints that may occur with standard supportive care, in the absence of active experimental treatment.

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: March 21, 2025
• Study Start: September 1, 2025
• Primary Completion: February 28, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 29, 2025

Record last verified: 2025-07